Chemo-Induced Neuropathy Common after Childhood Cancer

Neurotoxicity more prevalent in children treated with cisplatin

Chemotherapy-induced peripheral neuropathy is common in childhood cancer survivors and should be screened for in follow-up clinics, a cross-sectional analysis from Australia suggests.

Clinical abnormalities consistent with peripheral neuropathy occurred in about half of childhood cancer survivors 8.5 years after chemotherapy ended, with cisplatin producing long-term neurotoxicity more frequently than vinca alkaloids, reported Susanna Park, PhD, of the University of Sydney, and co-authors in JAMA Neurology.

"Traditionally, chemotherapy-induced peripheral neuropathy in children has been thought of as something that may occur during treatment but largely resolves in the long term. This study suggests that this is not the case," the study's first author, Tejaswi Kandula, MBBS, of the University of New South Wales in Sydney, told MedPage Today.

"Given that childhood cancers are on the rise, with an incidence of approximately 17 children per 100,000, this study is important because it shines a light on what could be an often-overlooked late effect of childhood cancer treatment," added Jonas Sokolof, DO, of New York University Langone's Rusk Rehabilitation, who was not involved with the research.

"We know that about 60% of all childhood cancer survivors will develop late effects," Sokolof told MedPage Today. While most of the emphasis has been on cardiac sequelae, infertility, and secondary cancers, "peripheral neuropathy, like many other late effects of childhood cancer treatment, has the potential to be very debilitating."

Neuropathy has been linked to common chemotherapy agents, including vincristine and other vinca alkaloids, cisplatin, and carboplatin. For this study, Kandula and colleagues recruited childhood cancer survivors who had been treated with chemotherapy before age 17 at Sydney Children's Hospital. They excluded patients with other causes of neuropathy including diabetes, critical illness neuropathy or inherited neuropathic conditions, and other neurodevelopmental disorders.

Of 121 childhood cancer survivors in the study, 53.7% were male. Participants underwent neurotoxicity assessments at a median age of 16 -- which was a median of 8.5 years after they completed treatment -- with results compared to healthy age-matched controls. Among cancer survivors, vinca alkaloids and platinum compounds were the main neurotoxic agents used.

Clinical abnormalities in Total Neuropathy Scores were present in 50.5% of childhood cancer survivors who were treated with neurotoxic chemotherapy. Lower limb sural sensory amplitudes were smaller in cancer survivors who were exposed to neurotoxic chemotherapy compared with controls (mean reduction of 5.8 μV; 95% CI 2.8-8.8; P<0.001), suggesting a reduced number of functioning axons. Patient-reported outcomes showed lower quality of life and physical functioning scores tied to Total Neuropathy Scores.

Overall, abnormalities were more prevalent in patients who had been exposed to cisplatin. Given the limited literature about cisplatin toxicity in pediatric patients, the discrepancy between vincristine and cisplatin toxicity found in this study makes cisplatin-treated patients an important population to follow, Kandula observed.

The researchers' finding that "half of childhood cancer survivors had clinically apparent chemotherapy-induced peripheral neuropathy is very similar to our recent report in adult women cancer survivors and should awaken clinical practice to address this neurotoxic side effect of cancer treatment," Kerri Winters-Stone, PhD, of Oregon Health and Science University in Portland, who was also not involved with the study, told MedPage Today.

Neuropathy's link to poorer quality-of-life scores in this analysis also is "distressing for young survivors because they have decades of education, work, and social plans ahead of them," Winters-Stone added.

Childhood cancer survivors are at high risk of cardiovascular disease and diabetes which may affect peripheral nerves later in life, Kandula noted, and "chemotherapy-induced peripheral neuropathy means these patients have a reduced axonal reserve and are potentially more at risk of early peripheral neuropathy when risk factors are compounded." Untreated neuropathy may hinder physical activity and compound future problems, but identifying neuropathy and prescribing physical therapy could help patients move and exercise more. The Total Neuropathy Score is "easily administered in less than 5 minutes and would make a good screening tool," Kandula suggested.

While this analysis "confirms the assumption that peripheral neuropathy frequently persists in many childhood cancer survivors," it provides only a snapshot of what these patients experience and does not reveal anything about cause and effect, Sokolof added.

The study was funded by grants from the National Health and Medical Research Council, the Cancer Institute of New South Wales, and funds from the Royal Australasian College of Physicians and Brain Sciences UNSW of the University of New South Wales, Sydney.

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